PUF Protein-mediated Deadenylation Is Catalyzed by Ccr4p

Goldstrohm, Aaron C.; Seay, Daniel J.; Hook, Brad; Wickens, Marvin

doi:10.1074/jbc.m609413200

Cited by 144 publications

(156 citation statements)

References 37 publications

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“…A study of the molecular mechanism by which the mRNA degradation machinery is recruited to target transcripts in S. cerevisiae revealed a role for the PUF family of mRNA binding proteins (12). A PUF family member in C. neoformans, Puf4, plays a role in host temperature adaptation, as a puf4⌬ mutant exhibits a temperature-sensitive growth phenotype and cell integrity defects (10).…”

Section: Discussionmentioning

confidence: 99%

Ccr4 Promotes Resolution of the Endoplasmic Reticulum Stress Response during Host Temperature Adaptation in Cryptococcus neoformans

et al. 2011

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Adaptation to host temperature is a prerequisite for any pathogen capable of causing deep infection in humans. Our previous studies demonstrated that a Cryptococcus neoformans ccr4⌬ mutant lacking the major deadenylase involved in regulated mRNA decay was defective in host temperature adaptation and therefore virulence. In this study, the ccr4⌬ mutant was found to exhibit characteristics of chronic unfolded-protein response (UPR) engagement in both the gene expression profile and phenotype. We demonstrate that host temperature adaptation in C. neoformans is accompanied by transient induction of the endoplasmic reticulum (ER) stress response and that Ccr4-dependent posttranscriptional gene regulation contributes to resolution of ER stress during host temperature adaptation.The pathogenic fungus Cryptococcus neoformans is one of two species of cryptococci commonly associated with infection in humans (2, 6). Unifying characteristics of the pathogenic cryptococci include the production of a polysaccharide capsule, the ability to form melanin pigments through the activity of the multicopper oxidase laccase, and the ability to adapt to and thrive at mammalian host temperature. Adaptation of C. neoformans to the host temperature is accompanied by major changes in gene expression as measured by microarray analysis and serial analysis of gene expression (SAGE) (5,19,29). This modulation of gene expression likely requires alterations in mRNA synthesis rates through activation of transcriptional transactivators and repressors, as well as alterations in chromatin structure. In addition to mRNA synthesis, our previous studies of a C. neoformans ccr4⌬ mutant lacking the major mRNA deadenylase involved in regulated mRNA turnover suggest a role for posttranscriptional regulation of gene expression in C. neoformans host temperature adaptation (24).Destabilization of specific transcripts in response to stress is highly conserved. In the model yeast Saccharomyces cerevisiae, deletion of CCR4 results in stabilization of transcripts encoding distinct functional classes (ribosome biogenesis, translation initiation, and tRNA synthesis) in response to temperature stress (13). In mammalian cells, subsets of transcripts were destabilized in response to heat shock, and induction of endoplasmic reticulum (ER) stress by treatment with tunicamycin or potentiation of ER calcium release by thapsigargin treatment triggered destabilization of a subset of mRNAs in which are included several transcripts encoding ribosomal proteins (8). This suggests that in response to heat shock and ER stress, distinct pools of transcripts representing specific cellular processes are targeted for degradation.The conserved ER stress response involves engagement of the unfolded-protein response (UPR) and the ER-associated degradation (ERAD) pathway (18). The UPR serves to retool the ER for enhanced protein folding, and ERAD serves to remove unfolded proteins from the ER lumen and shunt them into a degradative pathway. Microarray analyses performed in S. cerevisiae ...

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Section: Discussionmentioning

confidence: 99%

Ccr4 Promotes Resolution of the Endoplasmic Reticulum Stress Response during Host Temperature Adaptation in Cryptococcus neoformans

et al. 2011

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“…Because APUM23 is a nucleolar protein, it is possible that it has also other nucleolar functions such as rRnA byproduct degradation by exosome (3), a direct role in translation (4) or an indirect role via its role in ribosome biogenesis (5). Further, auxin and ribosome biogenesis are linked with each other such that defective ribosomes inhibit auxin biosynthesis [54][55][56] (6) and a local auxin accumulation can translationally repress ribosomal genes (7). 57 was supported by the Brain Korea 21 (BK21) program funded by the Ministry of Education, Science and Technology, Korea.…”

Section: Possible Protein Interaction Partners and Rnamentioning

confidence: 99%

“…Recent studies on Puf protein-mediated post-transcriptional processing uncovered the role of Puf proteins as cytoplasmic deadenylation cofactors. [4][5][6][7] De-adenylation of mRNA in eukaryotic cytoplasm accompanies translational repression and/or decay of mRNAs, and thus eventually regulates growth and development. In budding yeast, Puf4p and Mpt5 (Puf5p) are components of the Pop2p-Ccr4-Not de-adenylase complex, which removes the poly(A) tail of target mRNA and also recruits DExD/H-box helicase 1 (Dhh1p) and decapping enzyme 1 (Dcp1) for translational repression.…”

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confidence: 99%

Pumilio Puf domain RNA-binding proteins in Arabidopsis

Abbasi

Park

Choi

2011

Plant Signaling & Behavior

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“…Among the most affected transcripts are two that encode other RNA-binding proteins (Dhh1 and Mpt5), which are up-regulated by SSD1-V. Both of these proteins promote RNA decay via the Ccr4 complex (Garneau et al, 2007;Goldstrohm et al, 2007). DHH1 and SSD1 functionally complement each other¤ and double mutants are synthetically lethal (Moriya and Isono, 1999).…”

Section: Differentially Regulated Transcripts Of Genes That Interact mentioning

confidence: 99%

Budding YeastSSD1-VRegulates Transcript Levels of Many Longevity Genes and Extends Chronological Life Span in Purified Quiescent Cells

Qin

et al. 2009

MBoC

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Ssd1 is an RNA-binding protein that affects literally hundreds of different processes and is polymorphic in both wild and lab yeast strains. We have used transcript microarrays to compare mRNA levels in an isogenic pair of mutant (ssd1-d) and wild-type (SSD1-V) cells across the cell cycle. We find that 15% of transcripts are differentially expressed, but there is no correlation with those mRNAs bound by Ssd1. About 20% of cell cycle regulated transcripts are affected, and most show sharper amplitudes of oscillation in SSD1-V cells. Many transcripts whose gene products influence longevity are also affected, the largest class of which is involved in translation. Ribosomal protein mRNAs are globally down-regulated by SSD1-V. SSD1-V has been shown to increase replicative life span¤ and we show that SSD1-V also dramatically increases chronological life span (CLS). Using a new assay of CLS in pure populations of quiescent prototrophs, we find that the CLS for SSD1-V cells is twice that of ssd1-d cells. INTRODUCTIONSsd1 is an RNA-binding protein (Uesono et al., 1997;Hogan et al., 2008) that can be distinguished from the hundreds of other RNA-binding proteins by its unusual properties. First of all, ssd1 is highly pleiotropic. This locus has at least nine different names because of its having been identified in genetic screens for its effect on minichromosome stability, stress tolerance, membrane trafficking, and cell wall integrity, among other things Kosodo et al., 2001;Vannier et al., 2001;Reinke et al., 2004). Systematic global screens have identified ϳ200 genes that show genetic or physical interactions with Ssd1 (Reguly et al., 2006). These genes show a striking enrichment (Hong et al., 2008) for posttranslational modifiers (p ϭ 10 Ϫ14 ), including 19 kinases and nine histone deacetylases, and genes involved in the cell cycle and cell morphogenesis (p ϭ 10 Ϫ8 ). ssd1 mutants display sensitivity to high osmolarity, caffeine, fungicides¤ and numerous other compounds, which suggests a role for this protein in the maintenance of cell wall integrity (Ibeas et al., 2001;Parsons et al., 2004), but its mechanism of action remains obscure.Despite, or perhaps because of, its impact on so many different cellular functions, SSD1 is a common site of variation in both laboratory strains and natural populations of budding yeast (Wheeler et al., 2003). One possible explanation is that SSD1-V, which encodes the full-length "wildtype" protein, reduces the virulence of Saccharomyces cerevisiae in one mouse model (Wheeler et al., 2003), but SSD1-V is critical in Candida (Gank et al., 2008) and several fungal pathogens of plants for evading their hosts' defense systems (Tanaka et al., 2007). In most cases, genetic interactions with SSD1-V are positive, whereas the premature termination alleles (ssd1-d) cause lethality or a more extreme phenotype. One important exception is the RAM signaling pathway mutants, tao3 (Du and Novick, 2002), and cbk1 (Tong et al., 2001;Jorgensen et al., 2002), whose loss of function is lethal if the SSD1-V a...

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PUF Protein-mediated Deadenylation Is Catalyzed by Ccr4p

Cited by 144 publications

References 37 publications

Ccr4 Promotes Resolution of the Endoplasmic Reticulum Stress Response during Host Temperature Adaptation in Cryptococcus neoformans

Ccr4 Promotes Resolution of the Endoplasmic Reticulum Stress Response during Host Temperature Adaptation in Cryptococcus neoformans

Pumilio Puf domain RNA-binding proteins in Arabidopsis

Budding YeastSSD1-VRegulates Transcript Levels of Many Longevity Genes and Extends Chronological Life Span in Purified Quiescent Cells

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